One third of all smokers who make an annual quit attempt use one of the three FDA-approved pharmacotherapies (in contrast, <9% use behavioral intervention), but poor adherence is a well-documented problem for each of these medications. For example, we recently found that 50% of smokers taking varenicline had sub-optimal adherence. Non-adherence behavior such as inconsistent medication use, under-dosing, and early treatment discontinuation significantly undermines treatment effectiveness, which may in part explain why the great majority of treated smokers relapse. One way to improve the effectiveness of existing pharmacotherapy and to help more people stop smoking is to enhance treatment adherence. The current pilot study will evaluate the feasibility and acceptability of a prototype Internet-based medication adherence program (iMAP) from the perspective of smokers and clinicians (i.e., system users). iMAP is designed to facilitate ongoing communication between patients and clinicians; enhance adverse event monitoring; and provide 24/7 access to personalized support and encouragement, behavioral skills training for smoking cessation and medication adherence, and individually-tailored feedback on how to manage common, non-serious side-effects and nicotine withdrawal symptoms. iMAP can be accessed via personal computer or smartphone Internet browser. Given the popularity, high frequency of bothersome, non-serious medication side-effects, and increased monitoring demands for varenicline use, the pilot prototype is designed to support varenicline pharmacotherapy, but if the proposed intervention strategy proves promising, iMAP will be expanded to support nicotine replacement and bupropion use in the future. iMAP's design and content were informed by prior formative work with smokers and a team of clinical experts in medicine, clinical psychology, and pharmacy. The program will be tested in a small randomized study (n = 70) to assess users' reactions and estimate the program's potential impact on medication adherence and smoking cessation outcomes assessed over a 5 month period. [We will also interview clinicians (n ~ 50) to assess their reaction to the program's design and functionality. Outcomes from the clinician qualitative interviews and pilot trial will be shared with a clinical advisory board who will provie objective guidance about the feasibility of further developing the program and necessary program changes.] If the results prove promising, we will plan to refine the intervention as necessary and conduct a future randomized effectiveness trial to assess the program's impact on adherence, abstinence, and treatment cost-effectiveness. Findings from this work will help inform optimal ways to enhance medication adherence and, if effective, could help reduce smoking prevalence in the US, increase patient safety by addressing adverse events in a timely way, and improve treatment cost-effectiveness. Moreover, if effective, the proposed intervention model could be applied to the management of other medications (e.g., nicotine replacement, bupropion, others).